June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Therapy for Dry eye and Meibomian gland dysfunction(MGD) based on the replacement of (O-acyl)-omega-hydroxy fatty acids(OAHFAs)
Author Affiliations & Notes
  • Sher Li Gan
    School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, Singapore
  • Richard Webster
    School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, Singapore
  • Louis Tong
    Singapore Eye Research Institute, Singapore, Singapore
  • Roderick Bates
    School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, Singapore
  • Manfred Raida
    National University of Singapore, Singapore, Singapore
  • Footnotes
    Commercial Relationships   Sher Li Gan, None; Richard Webster, None; Louis Tong, None; Roderick Bates, None; Manfred Raida, None
  • Footnotes
    Support  Nanyang President's Graduate Scholarship conference allowance
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4385. doi:
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      Sher Li Gan, Richard Webster, Louis Tong, Roderick Bates, Manfred Raida; Therapy for Dry eye and Meibomian gland dysfunction(MGD) based on the replacement of (O-acyl)-omega-hydroxy fatty acids(OAHFAs). Invest. Ophthalmol. Vis. Sci. 2017;58(8):4385.

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      © ARVO (1962-2015); The Authors (2016-present)

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  • Supplements
Abstract

Purpose : The main aim of our work is to develop a supplementary form of dry eye treatment, that targets replacement of deficient lipid species in the tear film lipid layer(TFLL) induced by MGD. Based on the consistently decreasing trend of OAHFAs with increasing severity of dry eye and its amphiphilic nature, we propose a topical supplement of OAHFAs into the eye. This is an improvement from topical artificial tears, which remains the mainstay of dry eye treatment, but usually only provide temporary relief of symptoms for patients. The feasibility of this proposed treatment will be evaluated in healthy rabbits and dry eye models.

Methods : OAHFA 18:1/34:1 was selected to be synthesized as it showed a significant correlation with improved corneal staining after eyelid-warming treatment for MGD. Different formulations of the synthesized OAHFA are developed and selection was based on a study of the safety and retention time of the eye drops (30µL) tested on the rabbit's eye. Tear samples are collected at fixed intervals using Schirmer’s strips and HPLC/MS/MS studies are conducted to determine if the OAHFA eye drop is well retained in the eye and whether there are changes to the overall lipid profile upon application.

Results : OAHFA 18:1/34:1 was successfully synthesized via a convergent synthetic route (Scheme 1) and well characterised using NMR (1H and 13C), HRMS and elemental analysis. Two eye drop formulations were developed: (i) 0.1% OAHFA in undiluted olive oil (ii) emulsion of 0.1% OAHFA, 0.5% polysorbate 80, 1% glycerin, 1% olive oil in ultrapure water (aggregation size ~150 nm). Preliminary tests performed on a rabbit with (i) showed both no signs of irritation and a significant increase in OAHFA 5 minutes after application, along with a decrease in TAGs, PCs and DAGs as compared to controls instilled with olive oil only.

Conclusions : Preliminary results suggest that formulation (i) is not only well tolerated and retained in the eye but also triggered alteration to other lipid classes, hence implying that the eye drop may serve beyond a mere supplementation of OAHFAs in improving dry eye conditions. Similar tests will be conducted on more rabbits and further on with formulation (ii) to statistically determine the more suitable vehicle and dosage before proceeding on to pre-clinical trials on dry eye rabbit models for efficacy tests.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

Scheme 1. Synthesis of OAHFA 18:1/34:1

Scheme 1. Synthesis of OAHFA 18:1/34:1

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